tbuckley/cabot-search huggingface dataset:
Barriers and facilitators to implementing the Veterans Health Administration National Teleoncology Service: A qualitative descriptive study.
Authors: Heather King, Michael J. Kelley, Colleen Blue, Julie Miller, Whitney Raska, Gina McWhirter, John A. Pura, Amy Jeffreys, Leah L. Zullig
Journal: Journal of Clinical Oncology (2023)

e13684 Background: Many Veterans lack local access to specialized cancer services. When timely VA care is not accessible, the VA covers the cost of care provided in a Veteran’s community. This benefit disrupts integrated care delivery within VA and may be less applicable for Veterans in areas where specialized cancer services may also not be available locally. The National TeleOncology (NTO) service was established to provide remotely delivered cancer services and increase access for Veterans to specialized cancer care. We sought to understand early implementation experiences as part of an ongoing evaluation of the VA National TeleOncology (NTO) service. Methods: Informed by the Consolidated Framework for Implementation Research (CFIR), we conducted a qualitative descriptive study using virtual individual interviews with Veterans (results not reported) and focus groups with clinicians. To identify and describe implementation barriers and facilitators, oncologists, nurse practitioners (NPs), and registered nurses (RNs) who provide care via teleoncology were asked about the need for NTO, its advantages/disadvantages compared to alternatives, and how to operationalize and measure NTO’s success. Additionally, Veterans who have participated in the teleoncology program were asked about their experiences; the analysis of this data is ongoing. We employed a team-based, rapid qualitative analysis using structured forms for notetaking. Theme matrix techniques facilitated data analysis and presentation. Findings were mapped to CFIR domains and constructs. Results: Guided by information power, we conducted 15 individual interviews with Veterans and three focus groups, separated by clinician type. The individual interviews lasted approximately 36 minutes, and focus groups lasted approximately 30 minutes. Most Veteran participants were male (87%), white (60%), and had prostate cancer (47%). Results from our analysis suggest that clinicians feel there are key challenges/barriers to engaging NTO: 1) can delay care; 2) perception that NTO may not be as personable as in-person care; 3) technology access/use can be difficult for some Veterans. They also reported key advantages/facilitators: 1) provides Veterans nationwide with accessibility to cancer specialists; 2) keeps patients in VA system to support better care coordination and team-based care that expedites needed follow-up services. Conclusions: Those involved in implementing NTO feel supported and that it works well overall, especially to provide better coordinated cancer care for Veterans. These data will support an ongoing NTO evaluation. Separate data collection efforts are underway to understand the quality of care delivered to inform the widespread scale-out and delivery of NTO.
Evaluating the impact of a molecular tumor board in a community oncology center: Results from the Avera Cancer Institute's experience.
Authors: Rachel Elsey, Tobias Meissner, Yuliang Sun, Crystal Hattum, Heidi Ann McKean, Benjamin Maurice Solomon, David Starks, Luis Alexander Rojas-Espaillat, William Charles Spanos, John H. Lee, Casey B. Williams
Journal: Journal of Clinical Oncology (2023)

e13500 Background: The use of molecular tumor boards (MTB) has been widely documented at large academic medical centers, but there is limited experience and data available in smaller settings like community oncology centers. The Avera Cancer Institute has had a molecular tumor board in place since 2014, but the composition and methodology have changed over time. Our 10 years of hands-on experience and involvement in studies like I-PREDICT showed that in addition to molecular matching, considering factors like tumor type, previous treatment responses, comorbidities, medication coverage, and treatment availability provide crucial insights for determining optimal therapy for patients. Methods: We analyzed next-generation sequencing (NGS) testing results from August 2019 to December 2022. At the time of NGS testing result, providers were offered to have the case reviewed and presented at MTB. Our multidisciplinary team consists of members with backgrounds in bioinformatics, medical oncology, pathology, translational science, trial coordination, and pharmacy. Recommendations from the MTB discussions were provided in three categories: standard of care, clinical trials, and off-label options. Results: From August 2019 to December 2022, 1,514 qualified or resulted NGS reports were returned and considered for analysis. 733 (48%) were presented at the molecular tumor board and from this group, 629 patients were evaluable. Oncologists chose a recommended therapy 66% of the time. Of the remaining 34%, the most common reason for not utilizing recommendations was that patients were unable to receive further lines of systemic therapy. A subset analysis of 202 cases (June 2021 – August 2022) who either received a recommended therapy (n = 88, 43.6%, group 1) or not (n = 114, 56.4%, group 2) showed a survival benefit. Median overall survival was not reached in group 1, as compared with 14 months in group 2 (HR = 0.58; 95% CI, 0.37 – 0.92; p&lt; 0.02). The median PFS was 8.2 months in group 1 versus 5 months in group 2 (HR, 0.67; 95% CI, 0.48 - 0.92; p&lt; 0.017). Conclusions: The results of our study demonstrate the positive impact of a molecular tumor board review in helping oncologists determine the best treatment options for their patients. Our findings show that recommendations made by the board are well received and frequently adopted by providers. While providers generally prefer standard of care options or clinical trials, they are open to considering all available options to make informed therapy decisions.
Efficacy and safety of eribulin as a front-line treatment in patients with advanced breast cancer: The first large scale prospective real-world study in China.
Authors: Jianli Zhao, Xiao-Xiao Dinglin, Ya-Ping Yang, Si-Min Luo, Yang-Yang Cai, Jie Chai, Donggeng Liu, Ying Wang, He-Rui Yao
Journal: Journal of Clinical Oncology (2023)

e13127 Background: Eribulin is a non-taxane microtubule inhibitor, which was approved for third-line treatment of advanced breast cancer (ABC) in China in 2019. However, efficacy and safety data for eribulin in Chinese patients with ABC are lacking, regardless of the therapy line. This study evaluated the efficacy, safety, and treatment pattern of eribulin in first- to third-line settings in Chinese patients with ABC. Methods: Patients with histologically confirmed ABC who had received ≤2 lines of prior treatment for metastatic disease were enrolled. Patients with HR+/HER2- ABC received eribulin monotherapy; those with HER2+ ABC received eribulin plus anti-HER2 targeted therapy, and those with metastatic triple-negative breast cancer (mTNBC) received eribulin plus immunotherapy/chemotherapy. The primary outcome was progression-free survival (PFS). Secondary outcomes included disease control rate (DCR) and safety. This study was approved by the SYSMH and SYSUCC Ethics Committee (approval No. 2020-KY-064). Results: In total, 160 patients were enrolled from 1 January 2021 to 31 December 2022 and 142 received study treatment. Eribulin was administered as first-line therapy in 41 (28.9%) patients, second-line therapy in 50 (35.2%), and third-line therapy in 51 (35.9%). The DCR was 71.6%; 55 patients (45.8%) had stable disease and 31 patients (25.8%) had complete or partial remission. The 6-month PFS rates (95% confidence interval [CI]) were: overall, 68.4% (58.0%, 76.8%); first-line eribulin, 75.4% (54.9%, 87.6%); HR+/HER2- ABC, 67.4% (53.8%, 77.7%); HER2+ ABC, 70.1% (38.5%, 87.6%); mTNBC, 69.5% (46.3%, 84.2%). PFS data were immature; the median (range) PFS was not reached with first-line eribulin and was 11.8 (3.3, 11.8) months with second-line eribulin. Subgroup analyses are shown in the Table; the 6-month PFS rate was 64.3% versus 74.0% in patients with versus without visceral metastases (p=0.25364). Common treatment-related adverse events (AEs) were hematological toxicities including leukopenia (9.5%), neutropenia (5.3%), and hypochromia (7.3%). There were no grade ≥3 AEs or AE-related treatment discontinuations. Conclusions: There was no significant difference in the efficacy analysis between the subgroup with visceral metastases and the subgroup without visceral metastases. Eribulin as first- or second-line chemotherapy is effective and has manageable toxicity in patients with ABC. Clinical trial information: NCT04683445 . [Table: see text]
Longitudinal circulating tumor DNA monitoring in patients with esophageal squamous cell carcinoma.
Authors: Shogo Takei, Daisuke Kotani, Kazuma Sato, Naoto Fujiwara, Akihito Kawazoe, Shruti Sharma, Erik Spickard, Punashi Dutta, Minetta C. Liu, Adham A Jurdi, Kohei Shitara, Takashi Kojima, Takeo Fujita
Journal: Journal of Clinical Oncology (2023)

3041 Background: The clinical utility of longitudinal monitoring with circulating tumor DNA (ctDNA) as a prognostic and a predictive biomarker was recently reported in patients with resectable colorectal cancer (Kotani D, et al. Nature Medicine 2023). Here we report a prospective, observational study of longitudinal ctDNA monitoring in patients with esophageal squamous cell carcinoma (ESCC) receiving neoadjuvant chemotherapy (NAC) followed by surgery. Methods: Patients with ESCC planned for NAC followed by curative surgery, were prospectively enrolled in this study. As per the protocol, plasma samples were collected at 7 timepoints: pre-NAC, post-NAC, and 4,12, 24, 36, and 48-weeks after surgery. CT scans were conducted every 3 months. Longitudinal ctDNA testing was performed using a personalized, tumor-informed ctDNA assay (Signatera, bespoke mPCR, NGS assay). In this initial report, ctDNA results at 3 time points (pre-NAC, post-NAC, and 4 weeks post-surgery) were analyzed and their association with clinical outcomes and tumor regression grade (TRG) scores were assessed. Results: So far, a total of 83 blood samples from 28 patients with ESCC were collected serially at pre-NAC (N=28), post-NAC (N=27), and post-surgical (N=28) time points. Pre-NAC ctDNA was detectable in 96.4% patients (27/28), and detection rates decreased at the post-NAC (37%; 10/27) and post-surgical (11%; 3/28) timepoints. ctDNA-positivity post-NAC and post-surgery was associated with a significantly shorter recurrence free survival (RFS) with HR of 7.0 (95% CI: 1.4-35.0; p = 0.02) and HR of 14 (95% Cl 3.0-62; p &lt;0.001), respectively. Notably, patients who achieved ctDNA clearance with NAC had favorable RFS as compared to the patients who did not (HR=0.15, 95% CI: 0.03 – 0.75; p = 0.02). Post-NAC ctDNA was also associated with tumor regression grade (TRG) score. None of the patients with TRG3 score (N=3) were ctDNA positive, whereas 7.7% (1/13) patients in the TRG2 category and 81.8% (9/11) in the TRG1 category were ctDNA-positive. Conclusions: Our study demonstrates a strong correlation between ctDNA status and clinical outcomes in ESCC patients. Assessment of ctDNA may be useful monitoring in patients with ESCC post NAC/surgery and may be used in the future to direct post-surgical management in this patient population. Clinical trial information: UMIN000042003 .
The characteristics of metabolic related pathways under different anoikis activities revealed by pan-cancer analyses.
Authors: Shanshan Xiao, Yang Liu, Li Wang, Qian Wang, Tao Wang
Journal: Journal of Clinical Oncology (2023)

3150 Background: Anoikis is usually activated to eliminate extracellular matrix-detached cells. Cancers develop several mechanisms to escape from this cellular death signaling pathway which was associated with metabolic reprogramming in tumor development and progression. Comprehensively understanding the characteristics of anoikis activities in pan cancers facilitating better clinical treatment strategies. Methods: RNA-Seq data and related patient information were collected from 33 cancer types in TCGA database. We also obtained anoikis related genes (ARGs) from Harmonizome database. The related pathways of epithelial-mesenchymal transition (EMT) and reactive oxygen species (ROS) genes were collected from MSigDB. Autophagy genes were from HADb and metabolic intermediates were from published literatures. Firstly, pathway scores of anoikis and the related pathways were computed through single sample gene set enrichment analysis (ssGSEA). Then, survival analyses based on the anoikis scores were performed to achieve the threshold between the high anoikis (HA) or low anoikis (LA) sample groups. To study the drug efficacy, cell line transcriptome and IC50 data were obtained from GDSC database. Pearson correlations were computed between anoikis and other related pathways or immune cell infiltrations in each sample group. Results: Most ARGs were up-regulated in tumors, the same as the HA sample group. Differentially expressed genes between HA and LA were mostly involved in metabolic super-pathways, including metabolic intermediates (TCA cycle, carbohydrate, lipid, nucleotide, vitamin cofactor, and amino acid, etc.) and promoting anoikis-resistance pathways including EMT, inflammation and autophagy. Higher scores of anoikis related pathways were identified in HA across various cancers. Kaplan-Meier survival analysis revealed that HA in KIRC, KIRP, LAML, LGG, LUAD, PAAD, STAD, THYM, and UVM cancers had significantly worse clinical outcomes (p &lt; 0.05). Functional enrichment analysis of ARGs through GSEA suggested that anoikis resistance was promoted, whereas anoikis was retarded in those cancers. However, patients in HA of several cancers had longer survives than LA, which may owe to the higher infiltrating levels of anti-tumor immune cells including CD8+ T, CD4+ memory activated T cells, particularly in BRCA, MESO, SARC, and UCEC cancers. Drug efficacy analysis revealed that BCL2 gene was significantly associated with sensitive drug response on Venetoclax, ABT737, and Tozasertib. And TLE1 and CAV1 were associated with Tozasertib resistance and AZD5991 resistance, respectively. Conclusions: The characteristics of anoikis activities and metabolic related pathways during tumor progression were comprehensively studied and the prognosis value of anoikis was further assessed by drug efficacy.
Examination of in vitro and in vivo antitumor activity of Menin-MLL inhibitor, D0060-319.
Authors: Huan Xu, Yazhao Dai, Li Li, Hui Zhu
Journal: Journal of Clinical Oncology (2023)

e15119 Background: Rearrangements of the mixed-lineage leukemia (MLL) gene result in the production of MLL fusion proteins, which occurs in 5-10% of acute leukemia in adults and &gt; 70% of infant leukemia, respectively. Menin protein, encoded by the MEN1 gene, interacts with MLL fusion proteins to induce leukemia. D0060-319, a Menin-MLL inhibitor, shows a significant antitumor effect in vivo and in vitro. Methods: The fluorescence polarization (FP) binding assay to assess inhibition of D0060-319 to Menin-MLL interaction. The cross reactivity of 44 molecular targets was tested to assess their off-target binding potential. The anti-proliferative ability of D0060-319 was evaluated by CCK-8 in different cell lines. The in vivo anti-tumor effect of D0060-319 was evaluated in a human MV4-11 and MOLM-13 cell mouse xenograft tumor model. Briefly, five million MV4-11 cells or 500 thousand MOLM-13 cells were subcutaneously implanted the right flank of CB-17 SCID mice to establish cell mouse xenograft tumor model. When tumor volume reached 100-120mm 3 , the animals were grouped and administrated with D0060-319 at the dose of 25, 50, 75, 100 mg/kg or vehicle at twice daily for 21days. Tumor measurements and body weights were performed twice weekly to assess the antitumor efficacy and tolerability of D0060-319. Results: D0060-319 competitively binds Menin to inhibit the interaction with MLL fusion protein with IC50 of 7.46nM, has high antiproliferative activity in MV4-11 and MOLM-13 cell lines containing MLL fusion proteins with IC50 values of 4.0nM and 1.7nM, respectively. However, in Kasumi-1, K562, HL-60 and KG-1 cell lines lacking MLL rearrangement, D0060-319 antiproliferative activity with IC50 &gt; 10 μM, indicating selectivity for leukemia cell lines containing MLL fusion proteins active. In the MV4-11 cell mouse xenograft tumor model, D0060-319 significantly inhibited tumor growth at the dose of 25mg/kg, with a tumor growth inhibition (TGI) rate of 82.97%, and other doses (50, 75 and 100mg/kg) tumor completely regressed. In the MOLM-13 cell mouse xenograft tumor model, a dose-dependent anti-tumor effect was observed after 14 days of administration, with TGIs of 81.08%, 88.47% and 90.26% at the dose of 50, 75 or 100 mg/kg, respectively. In both CDX models, no bodyweight loss was observed, suggesting that D0060-319 was well tolerated. Furthermore, off-target screening assays showed that D0060-319 did not cross-react with any of the 44 molecular targets at 10 μM, indicating that D0060-319 is highly selective, high-affinity for the MLL-binding pocket on Menin. Conclusions: In MLL-rearranged leukemia, D0060-319 showed high antitumor activity and good tolerability both in vitro and in vivo.
Association of Medicaid expansion with treatment receipt, delays in treatment initiation, and survival among young adult women with breast cancer.
Authors: Xuesong Han, Kewei Sylvia Shi, Kathryn Jean Ruddy, Jingxuan Zhao, Ann C. Mertens, Robin Yabroff, Sharon M. Castellino, Xu Ji
Journal: Journal of Clinical Oncology (2023)

1509 Background: Medicaid expansion under the Affordable Care Act has been shown to increase insurance coverage and early-stage cancer diagnoses for young adults (YAs), the age group with the highest uninsured rate. We examined whether Medicaid expansion was associated with increased receipt of timely, guideline-concordant treatment and survival among YA women newly diagnosed with breast cancer, the most common YA cancer diagnosis. Methods: Using the National Cancer Database, we identified 51,675 women aged 18-39 years who were diagnosed with breast cancer in 2011-2018. We applied the difference-in-differences (DD) method to estimate outcome changes pre vs. post Medicaid expansion, in expansion- vs. non-expansion states. Linear probability models estimated associations of Medicaid expansion with receipt of guideline-concordant treatment – including any endocrine therapy among women with ER-positive or PR-positive breast cancer, and any chemotherapy or targeted therapy among women with ER-negative and PR-negative breast cancer – and initiation of guideline-concordant treatment (surgery, chemotherapy, or targeted therapy for stage I-III diagnoses, and systemic therapy for stage IV diagnoses) &lt;60 days after diagnosis. Flexible parametric survival models were used to estimate 2-year overall survival. DD models also adjusted for age, race/ethnicity, rurality, zip code-level income, comorbidity, and diagnosis year, with standard errors clustered at the state level. Analyses were stratified by stage at diagnosis (stage I-III vs. IV). Results: Of the subset of women with stage I-III ER-positive or PR-positive breast cancer, the percentage receiving endocrine therapy increased in expansion states (85.20% pre-expansion to 86.46% post-expansion), but decreased in non-expansion states (84.32% to 82.79%), resulting in a net increase of 2.42 percentage points (ppt; 95% CI = 0.56 to 4.28) associated with Medicaid expansion in the adjusted DD model. Among all women with stage I-III breast cancer, the percentage with treatment initiation &lt;60 days after diagnosis decreased less in expansion states (84.10% pre-expansion to 82.36% post-expansion) than in non-expansion states (86.95% to 83.98%), resulting in a net reduction of 1.61 ppt (95% CI = 0.05 to 3.18) in treatment delays associated with Medicaid expansion. Notably, the 2-year overall survival increased in expansion states (96.84% pre-expansion to 96.99% post-expansion), but decreased in non-expansion states (97.24% to 96.30%), resulting in a net survival increase of 1.00 ppt (95% CI = 0.21 to 1.79) associated with Medicaid expansion. Conclusions: Among YA women with stage I-III breast cancer, Medicaid expansion was associated with increased receipt of guideline-concordant treatment, reduced delays in treatment initiation, and improved 2-year survival.
Body composition measures as predictors of toxicity in patients with metastatic breast cancer receiving PARP inhibitors.
Authors: Tal Etan, Rivka Kessner, Shira Peleg Hasson, Ari Raphael, Amir Sonnenblick, Noa Zlothover, Jessica Epstein, Shlomit Strulov Shachar
Journal: Journal of Clinical Oncology (2023)

e13010 Background: Poor body composition metrics (BCM), such as high adiposity or low muscle mass, are associated with inferior cancer outcomes. Poly ADP-ribose polymerase inhibitors (PARPi) revolutionized the treatment of metastatic breast cancer (MBC) with germline BRCA mutation but can cause substantial toxicity. The recommended dose of PARPi is fixed and neither weight nor BCM are taken into consideration during initial prescription or during dose reductions. We aimed to investigate the association between BCM and toxicity and tolerability to PARPi in MBC patients. Methods: We identified all MBC patients treated with PARPi between 2015-2022 at Tel Aviv Sourasky Medical Center. Using computerized tomography (CT) images taken for the evaluation of disease burden, BCM such as: skeletal muscle area (SMA) and subcutaneous adipose tissue area (SAT), were measured at the level of the third lumbar (L3) vertebrae. Low SMA was defined as &lt; 107.2 cm 2 and low SAT was defined as &lt; 190 cm 2 . Receiver operating characteristic (ROC) curves were used to define these thresholds. Sarcopenia was defined as skeletal muscle index (SMI = SMA/height 2 ) &lt; 41 based on literature. Fisher exact tests and Mann-Whitney U tests were used for statistical analyses. Results: We identified 30 patients with MBC who were treated with PARPi and met the study requirements at a median age of 54 (range 29-87). Median duration of PARPi treatment was 214 days (range 35-921). Among them, 19 (63%) were sarcopenic, 22 (73%) had low SMA, 10 (33%) had low SAT and 17 (57%) suffered from Grade 2-4 adverse events (AE). Patients with sarcopenia had non-significantly more Grade 3-4 AE (42% vs. 18%) and more dose reduction or dose delay events (42% vs. 27%) compared to non-sarcopenic patients. Patients with low SMA had borderline significantly more Grade 3-4 AE, dose reduction or dose delay events (55% vs. 13%, p = 0.065), compared to patients with high SMA. Patients with low SAT had significantly more Grade 3-4 AE (60% vs 20%, P = 0.036), compared to patients with high SAT. Moreover, patients with Grade 2-4 AE had significantly lower SAT compared with patient with &lt; Grade 2 AE (median 183 vs. 298 cm 2 , p = 0.008). Conclusions: Our study implies an association between BCM and PARPi toxicity and tolerability. Skeletal muscle mass and adipose tissue may be taken into consideration in PARPi treatment and dosing decisions. A larger study is needed to further examine this hypothesis.